Technical Abstract:
Campylobacter jejuni is a leading cause of food- and waterbourne bacterial gastroenteritis in the developed world. Although illness is usually self-limiting, immunocompromised individuals are at risk for infections recalcitrant to antibiotic treatment, and prior campylobacter infection correlates with serious sequelae such as Guillain-Barre syndrome. Thus, both the high incidence and severity both contribute to the significant burden of C. jejuni infections, and development of strategies limiting infection may reduce the impact of C. jejuni.
Despite its apparent fastidiousness and fragility in the lab, the success of C. jejuni indicates it possesses mechanisms for surviving varied conditions encountered during pathogenesis, and understanding such mechanisms may allow us to limit survival in environmental reservoirs. We previously identified a putative two-component regulatory system, CprRS (Campylobacter planktonic growth regulation), as upregulated during cell infections in vitro. Ongoing characterization of CprRS through whole-genome expression (proteomics; microarrays) and molecular approaches and has confirmed that CprRS contributes to host colonization and allowed us to understand two themes of C. jejuni survival: biofilm formation and environmental gene regulation. Analysis of a biofilm-enhanced 'cprS sensor kinase mutant has identified the importance of extracellular DNA, cell lysis, envelope stress, and flagella in biofilm formation. The CprR response regulator is also confirmed as essential in vitro, suggesting a role in controlling essential biological processes and necessitating elaborate genetic characterization which has yielded a greater understanding of gene regulation in C. jejuni. This has included promoter identification and analysis, construction of phosphoaspartate-null point mutants, and one-hybrid identification of the CprR binding consensus sequence.
Characterization of CprRS has thus contributed to our knowledge of both physiological and regulatory themes in survival of C. jejuni during pathogenesis and is identifying factors that may serve as novel targets for infection control in a pathogen which diverges from the accepted paradigms set out in model bacteria.